Disease relevance of Lacidipine

• Although lacidipine limited hypertension, it did not reduce proteinuria or prevent tubular atrophy and disconnection [1].
• BACKGROUND: In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4-year antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment [2].
• OBJECTIVES: This study was designed to investigate the acute direct effects of repeated infusions of lacidipine on epicardial coronary artery vasomotion and on post-stenotic coronary artery blood flow in patients with stable angina pectoris and angiographic evidence of coronary heart disease [3].
• The reduction in left ventricular hypertrophy (LVH) is an obvious goal of antihypertensive therapy, and several studies have demonstrated the effectiveness of lacidipine treatment in decreasing LVH in hypertensive patients [4].
• CONCLUSIONS: These results suggest that lacidipine acts directly as a potent vasodilator in stenotic epicardial vessels and improves myocardial perfusion distal to a moderately severe stenosis in patients with stable angina [3].

Psychiatry related information on Lacidipine

• OBJECTIVE: The main objective of this study was to evaluate well-being and physical activity of 248 hypertensive patients, including 177 females, who had previously been included in the Latin-American Study on Lacidipine in Hypertension (LASTLHY) [5].

High impact information on Lacidipine

• Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients [6].
• In comparison with placebo, lacidipine produced a significant decrease in blood pressure, together with systemic and carotid arteriolar dilatation [7].
• Quality control of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis [8].
• The aim of this 2-year study was to assess the effects of lacidipine on graft function (plasma iohexol clearance), renal plasma flow, anastomotic arterial blood flow, deterioration of renal function, blood pressure, acute rejection, and hospitalization rate [9].
• OBJECTIVE(S): To study the changes in macrophage inducible nitric oxide synthase (iNOS) activity, plasma levels of nitrite, lipid peroxidation (LPO) and melatonin in human essential hypertension before and 6 months after 4 mg/day lacidipine treatment [10].

Chemical compound and disease context of Lacidipine

• OBJECTIVE: To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension [11].
• The lowest dosage of lacidipine (but not of amlodipine) restored the physiological downregulation of renin production by high salt and reduced left ventricular hypertrophy and mRNA levels of atrial natriuretic factor and transforming growth factor-beta1 [12].
• We have previously shown that lacidipine, a dihydropyridine-type calcium antagonist, reduced the cardiac hypertrophy and the cardiac endothelin-1 (ET-1) gene overexpression occurring in salt-loaded stroke-prone spontaneously hypertensive rats (SL-SHRSP), an effect occurring without systolic blood pressure (SBP) change [13].
• METHODS AND RESULTS: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL [14].
• The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy [15].

Biological context of Lacidipine

• Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered [11].
• Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine [16].
• CONCLUSIONS: Lacidipine exhibited linear kinetics after repeated doses in the therapeutic range of 2-6 mg once daily [17].
• CONCLUSIONS: The results suggest that the resetting of the baroreflex after the acute reduction in blood pressure caused by lacidipine is dissociated from mechanical changes in the carotid artery wall [18].
• OBJECTIVE: To assess the dose proportionality of lacidipine after single and repeated oral doses, and to obtain new information on the pharmacokinetics of the compound since improvement of the plasma assay method [17].

Anatomical context of Lacidipine

• METHODS: In 8 patients with stable angina and moderate to severe stenosis of the left coronary artery, measurements of epicardial dimensions (quantitative angiography) and of coronary blood flow (Doppler guidewire) distal to a stenosis were performed at baseline and after 3 repeated intracoronary boluses of 12 microg of lacidipine [3].
• Oxidized low-density lipoprotein increases the production of intracellular reactive oxygen species in endothelial cells: inhibitory effect of lacidipine [19].
• Between-group differences in favour of lacidipine for the primary efficacy variable (mean change in carotid artery intima-media thickness) did not reach statistical significance in the intent-to-treat population [20].
• Moreover, lacidipine reduced circulating markers of oxidative stress including plasma and low-density lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced oxidation and the reactive oxygen species generated from human umbilical vein endothelial cells after incubation with LDL derived from plasma of the patients [21].
• Thus, lacidipine reduced blood pressure and free radicals, avoiding the oxidative damage to endothelium [10].

Associations of Lacidipine with other chemical compounds

• In addition to calcium channel-modulated vasodilation, lacidipine displays antioxidant activity greater than that of other dihydropyridine calcium antagonists [20].
• Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases [11].
• INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities [22].
• Effects of amlodipine and lacidipine on cardiac remodelling and renin production in salt-loaded stroke-prone hypertensive rats [12].
• Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits [23].

Gene context of Lacidipine

• The lowest IC50, i.e. the concentration determining the 50% reduction of ICAM-1, VCAM-1 and E-selectin expression was obtained with lacidipine for all the adhesion molecules considered (P < 0.01) [24].
• Finally, peritoneal macrophages, obtained from mice treated with lacidipine, showed a reduced secretion of MMP-9 [25].
• Lacidipine reduced also the secretion of the tissue inhibitor of metalloproteinase-1 (TIMP-1); however we observed an overall reduction of the gelatinolytic activity of the cells [25].
• Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin-1 gene expression in stroke-prone hypertensive rats [13].
• 4. The maximum binding capacity (Bmax) and the dissociation constant (KD) of [125I]-ET-1 binding and the relative proportion of low- and high-affinity binding sites for ET-3 were not significantly affected by salt loading or lacidipine treatment in SHRSP [13].

Analytical, diagnostic and therapeutic context of Lacidipine

• Systemic and carotid hemodynamics were studied in 10 healthy male volunteers before and after short-term administration of a 4 mg dose of the calcium entry-blocker lacidipine in a placebo-controlled, double-blind, crossover study [7].
• BACKGROUND: The calcium antagonist lacidipine has been shown to be highly vasoselective and to improve myocardial perfusion in hypertensive patients [3].
• Previous studies have demonstrated the ability of lacidipine to reduce the development of atherosclerotic lesions in several animal models [26].
• Structural changes of small resistance arteries in spontaneously hypertensive rats after treatment with various doses of lacidipine [27].
• In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies [28].

References